Cervical cancer was previously the leading cause of cancer-related death among women in the US; however, incidence and mortality have decreased by >70% due to the introduction of screening programs to detect early cervical cancer and its precursors. In stark contrast, cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle-income countries (LMICs). There is a significant need for appropriate cervical cancer screening and diagnostic tools that can be used in resource- limited settings. The World Health Organization's recommendations for cervical cancer prevention methods in low-resource settings focus on screen-and-treat strategies using visual inspection with acetic acid (VIA) or HPV testing, alone or in combination. However in many large studies, the positive predictive value of VIA and HPV testing have been found to be <10%. Thus, based on VIA or HPV screening alone, >90% of women with a positive test result would be inappropriately treated in a see-and-treat setting. Here, we propose to optimize and validate a high resolution microendoscope (HRME) to be used in see- and-treat programs to improve specificity without reducing sensitivity. The goal of this application is to optimize and validate the performance of the HRME for real-time diagnosis of cervical cancer in urban and rural settings in Brazil. In the UH2 phase, we will demonstrate successful implementation of the HRME in a novel mobile diagnostic and treatment unit for real-time diagnosis and treatment of cervical precancer in screen-positive women in a single visit in order to reduce the number of women lost to follow-up. In the UH3 phase, we will carry out a study involving over 12,000 women to validate that the HRME has improved diagnostic sensitivity and specificity compared to VIA and colposcopy for combined diagnosis and treatment in a single visit. Our project will validate the use of HRME as a real-time, in vivo diagnostic tool that can b applied in a variety of scenarios as an alternative to the traditional diagnostic methods of colposcopy and biopsy, which are impractical in many LMICs. Our team includes expertise in bioengineering (Rice University) and cervical cancer prevention and treatment (UT MD Anderson Cancer Center and Barretos Cancer Hospital). Our teams have worked together for two years to develop affordable, effective technologies for cervical cancer prevention in low-resource settings. To ensure that results of this work lead to sustainable implementation and scale-up within and beyond Brazil, we are teamed with the Global Coalition Against Cervical Cancer, an NGO that assists LMICs in the implementation of comprehensive, sustainable, and effective cervical cancer prevention and control. Our development partner is Becton Dickinson, a multi-national medical technology company with a strong commitment to global efforts to improve women's health.